ELSEVIER Nicotine-Haloperidol Interactions and Cognitive Performance in Schizophrenics Edward D. Levin, Ph.D., William Wilson, Ph.D., Jed E. Rose, Ph.D., and Joseph McEvoy, M.D. Nearly 90% of schizophrenics smoke cigarettes, considerably higher than the general population's rate of 25%. There is some indication that schizophrenics may smoke as a form of self-medication. Nicotine has a variety of pharmacologic effects that may both counteract some of the cognitive deficits of schizophrenia and counteract some of the adverse side effects of antipsychotic drugs. In the current study, we assessed the interactions of haloperidol and nicotine on cognitive performance of a group of schizophrenics. These patients were in a double-blind study, randomly assigning them to low, moderate, and high dose levels of haloperidol. The subjects, all smokers, came to the laboratory on four different mornings after overnight deprivation from cigarettes. In a double-blind fashion, they were administered placebo, low (7 mg/day), medium (14 mg/day), or high (21 mg/day) dose nicotine skin patches. Three hours after administration of the skin patch, the KEY WORDS: Nicotine; Haloperidol; Memory; Reaction time; Schizophrenia The very high rates of cigarette smoking among schizo- phrenics, nearly 90%, has been noted in a variety of studies (Hughes et al. 1986; O'Farrell et al. 1983). Over the past 30 years, smoking in the general population in the United States has declined to about 25% (Fiore 1992), but the smoking rates in certain groups including From the Department of Psychiatry (EDL, WW, JER, JM) and Department of Pharmacology (EDL), Duke University Medical Cen- ter, Department of Research Service, VA Medical Center (JER), Durham, North Carolina. Address correspondence to: Dr. Edward D. Levin, Neurobehav- ioral Research Laboratory, Department of Psychiatry, Box #3412, Duke University Medical Center, Durham NC 27710. Received August 21, 1995; revised September 28, 1995; accepted January 5, 1996. NEUROPSYCHOPHARMACOLOGY 1996-VOI.. 15, NO. 5 © 1996 American College of Neuropsychopharmacology Published by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 subjects were given a computerized cognitive test battery including: simple reaction time, complex reaction time (spatial rotation), delayed matching to sample, the Sternberg memory test, and the Conners continuous performance test (CPT). With the placebo nicotine patch, there was a haloperidol dose-related impairment in delayed matching to sample choice accuracy and an increase in response time on the complex reaction time task. Nicotine caused a dose-related reversal of the haloperidol-induced impairments in memory performance and complex reaction time. In the CPT, nicotine reduced the variability in response that is associated with attentional deficit. These results demonstrate the effects of nicotine in reversing some of the adverse side effects of haloperidol and improving cognitive performance in schizophrenia. © 1996 American College of Neuropsychopharmacology [Neuropsychopharmacology 15:429-436, 1996] schizophrenics remains high. Nicotine, the principal psychoactive ingredient in tobacco, has a wide variety of pharmacologic effects. Some of these effects such as cognitive enhancement can be beneficial, despite the other adverse health consequences of tobacco use. Some smokers might use tobacco as a form of self-medication. It seems most likely that groups who smoke most heavily may be most likely to be engaging in self-medi- cation. Several lines of evidence point to the likelihood for nicotine self-medication in schizophrenics (Lohr and Flynn 1992). The current study was conducted to deter- mine the pharmacologic effects of nicotine on cognitive function in schizophrenics, whether it might reverse some of the cognitive deficits associated with schizo- phrenia and as well as deficits that result from antipsy- chotic medication. Nicotine has been widely shown to be very effective in stimulating dopamine (DA) release (Andersson et al. 0893-133X/96/$15.00 PII S0893-133X(96)00018-X